ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.14C>T (p.Pro5Leu) (rs530517936)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588536 SCV000697883 uncertain significance not provided 2017-01-03 criteria provided, single submitter clinical testing Variant summary: The DSG2 c.14C>T (p.Pro5Leu) variant involves the alteration of a non-conserved nucleotide, which 2/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP), nor has it been, to our knowledge, reported in affected individuals via publications and/or clinical diagnostic laboratories/databases. Therefore, until additional information becomes available (ie, clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)."
Ambry Genetics RCV000619285 SCV000737791 uncertain significance Cardiovascular phenotype 2016-11-09 criteria provided, single submitter clinical testing The p.P5L variant (also known as c.14C>T), located in coding exon 1 of the DSG2 gene, results from a C to T substitution at nucleotide position 14. The proline at codon 5 is replaced by leucine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase (dbSNP) as rs530517936, but was absent from population based-cohorts in the Exome Aggregation Consortium (ExAC), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project databases. In the ESP, this variant was not observed in 5552 samples (11104 alleles) with coverage at this position, but sequencing depth was low. This amino acid position is poorly conserved in available vertebrate species, and leucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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